24,042 research outputs found
The cathepsin D Gene Exon 2 Polymorphism and sporadic Alzheimer's disease in European Population
No full textInterleukin 6 -174 G/C promoter gene polymorphism in centenarians: No evidence of association with human longevity or interaction with apolipoprotein e alleles
No full textInterleukin 6 variable number of tandem repeats (VNTR) gene polymorphism in centenarians
No full textInterleukin 6-174 G/C promoter gene polymorphism and sporadic Alzheimer's disease: geographic allele and genotype variations in Europe
No full textThe interleukin 6 (IL-6) gene in humans is located in the short arm of chromosome 7 and has a-174 G/C polymorphism in its promoter
region. The C allele at position-174 in the promoter of the interleukin 6 (IL-6) gene has been associated with reduced gene expression and
reduced plasma levels of IL-6. Given the supposed role of several inflammatory mediators in neurodegeneration and Alzheimer’s disease
(AD), the IL-6-174 G/C promoter polymorphism has been associated with AD with contrasting findings. First aim of the present study was to
investigate whether there was evidence in Southern Italy of an association between the IL-6-174 G/C promoter polymorphism and AD.
Secondly, we also tested a possible effect of geographic genetic variations on existing reported associations comparing our results with the
findings from published studies on other European populations. We examined apolipoprotein E (APOE) and IL-6-174 G/C promoter
polymorphisms in a cohort of 168 sporadic AD patients and 220 sex- and age-matched nondemented controls from Southern Italy. No
differences have been found in the IL-6-174 G/C promoter allele and genotype frequencies between AD patients and controls nor in early and late-onset subsets of AD patients. No statistically significant differences in frequencies between IL-6-174 G/C promoter alleles and AD among APOE allele strata were found. Finally, comparing our results with the findings from other European populations, the IL-6*G/*G genotype frequency showed a statistically significant increasing trend from Northern to Southern regions of Europe in AD patients and controls, with a concomitant increase in IL-6*C/*G genotype frequency. Furthermore, an increasing geographical trend from North to South was found for the IL-6*G allele, with a concomitant inverse trend for IL-6*C allele. We suggest that regional European differences in genotype and allele frequencies of the IL-6-174 G/C promoter polymorphism may explain in part controversial findings on this polymorphism in AD in various European studie
Cardiovascular risk and prevention in the elderly: Role of n-3 PUFA [Rischio e prevenzionecardiovascolare nell'anziano: Ruolo dei PUFA n-3]
No full textMacronutrients, aluminium from drinking water and foods, and other metals in cognitive decline and dementia
No full textInterleukin 6 variable number of tandem repeats (VNTR) gene polymorphism in centenarians.
No full textRecent population-based studies identified the magnitude of interleukin 6 (IL6) serum levels as a marker for functional
disability, and a predictor of disability and mortality among the elderly. We investigated whether there was evidence in
Southern Italy of an association between the IL6 gene variable number of tandem repeats (VNTR) polymorphism and
extreme longevity, and tested for the possible interaction of apolipoprotein E (APOE) alleles with the IL6 VNTR alleles.
Four alleles coding for variants of four different lengths have been identified: allele A [760 base pairs (bp)], allele B (680 bp),
allele C (640 bp), and allele D (610 bp). IL6 VNTR and APOE allele and genotype frequencies were studied in a total
of 61 centenarians and 94 middle-aged subjects from Southern Italy. The IL6 VNTR allele B was overrepresented in the
younger control group compared with centenarians (odds ratio: 0.56, 95% confidence interval: 0.35–0.88, Bonferroni
p-value < 0.05). No interactions between IL6 VNTR alleles and APOE alleles on the odds ratios to reach extreme
longevity were evaluated for the smallest number of subjects in centenarians and younger controls. Our findings suggested
that the presence of the IL6 VNTR allele B could be detrimental for reaching extreme longevity
Interleukin 6-174 G/C promoter gene polymorphism in centenarians: no evidence of association with human longevity or interaction with apolipoprotein E alleles.
No full textThe C allele at position 2174 in the promoter of the interleukin 6 (IL-6) gene has been associated with reduced gene expression and
reduced plasma levels of IL-6. Given that IL-6 tracks with functional disability and age-related diseases, there may be attrition or reduction in
the frequency of the homozygous subjects, who produce higher IL-6 serum levels, in older survivors in a population. In fact, a marked
reduction of the IL-6*G/*G genotype was recently demonstrated in male though not female Italian centenarians compared with younger age groups. First aim of the present study was to investigate whether there was evidence of an association among IL-6 2174 G/C promoter polymorphism and extreme longevity in a population of 81 centenarians compared with a control group of 122 middle-aged healthy subjects (mean age: 51 ^ 18 SD; range: 19–73 years), from Apulia (Southern Italy). Secondly, we also tested possible interaction of apolipoprotein E (APOE) alleles with the IL-6 2174 G/C promoter polymorphism in view of our recent findings for reduced APOE 14 allele in centenarians. No differences have been found in the IL-6 2174 G/C promoter allele and genotype frequencies between centenarians and controls nor was there any observed interaction with APOE alleles that are also reputed to be linked to longevity. Regional genetic differences in conjunction with differing environmental factors may explain in part previous results suggesting a role of this polymorphism in longevity
Candidate genes for late-onset Alzheimer's disease: focus on chromosome 12
No full textIn recent years, there was an increasing interest on candidate genes may play an important role in the development of Alzheimer’s disease (AD).
Several genome wide screens have undertaken so far or expanded recently, and suggested a number of genomic areas that may contain novel
susceptibility genes for AD, in particular most compelling have been the findings on chromosome 12. Polymorphisms in different susceptibility
genes on chromosome 12 (A2M, LRP1, CP2 and OLR1) are now being suggested as possible genetic markers for increased risk of developing AD.
However, many of these studies are controversial and have shown conflicting results. Thus far, the search for the chromosome 12 Alzheimer’s gene
must continue and there are several other genes in this region that we are looking at. In this article, we focused on the current knowledge of the
genetics of familial late-onset and sporadic AD linked to the chromosome 12, and the future search for other candidate genes.
# 2005 Elsevier Ireland Ltd. All rights reserved
Lipid metabolism in cognitive decline and dementia
No full textThis review will focus on the current knowledge on circulating serum and plasma risk factors of cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD) linked to cholesterol homeostasis and lipoprotein disturbances, i.e. total cholesterol (TC), 24S-hydroxy-cholesterol, lipoprotein(a) (Lp(a)), or apolipoprotein E (APOE). These measures linked to lipoprotein metabolism appear to be altered in AD, VaD, or predementia syndrome relative to controls, but with contrasting results. At present, several studies have demonstrated the dependence of APOE serum levels upon the APOE genotype, nonetheless serum APOE levels seems not to be a credible risk factor or a biochemical marker for AD instead of APOE genotyping. In fact, there was no consistent association of serum or plasma apoE protein levels with the disease when controlled for APOE genotype. In addition, there are some evidence that higher Lp(a) levels could be linked with AD, although there are studies suggesting an increased presence of low molecular weight apo(a) in AD, VaD, and frontotemporal dementia, that are associated with elevated Lp(a) levels. In fact, the apo(a) gene is highly polymorphic in length due to variation in the numbers of a sequence encoding the apo(a) kringle 4 domain, and plasma levels of Lp(a) are inversely correlated with apo(a) size. Furthermore, although serum/plasma levels of TC and 24S-hydroxycholesterol are not credible diagnostic markers for AD and cognitive decline, the current evidence suggests that they may be modifiable risk/protective factors. The prevailing wisdom is that high TC is a risk factor for dementia. However, the relationship between TC and dementia may vary considerably depending on when cholesterol is measured over the life course or, alternatively, in relation to the underlying course of the disease. Several observational studies have suggested that statins, which are effective in lowering cholesterol, may reduce the risk of dementia, but the results of these reports are inconclusive. Thus, more studies with long-term follow-up and serial assessments of TC are needed to further clarify the causal relationship between cholesterol and dementia
- …
